Our primary objective is to compare the clinical outcome (time to and grade of symptom resolution) after 4-week-use of a whey based extensively hydrolysed formula (eHF) versus an amino acid-based formula (AAF) in children with nIgE-CMA. As secondary…
ID
Source
Brief title
Condition
- Gastrointestinal disorders
- Allergic conditions
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
The main study endpoints of the study are time to symptom resolution and grade
of symptom resolution after 4 weeks of treatment. The data collected at the
phone call after 2 weeks of treatment will also be taken into account.
Secondary outcome
As secondary objectives we will assess:
- Parent-reported data on symptoms and formula intake during the elimination
period
- Number of failures and remissions in each study arm (based on the symptom
score)
- Time point of acquired tolerance
- Clinical effect markers; which subjects needed additional treatment with AAF
to resolve their symptoms?
- Biomarkers of (gut) inflammation
- Immune status
- Tolerance markers
- Microbiome
- Quality of Life (measured through the FAQLQ-PF: the food allergy related
quality of life questionnaire for parents of children aged 0 - 12 years)
Background summary
The guidelines used for the diagnosis and management of cow*s milk allergy
(CMA) are largely based on research in children with the classical phenotype of
IgE-mediated allergic disease. These guidelines do not focus on
non-IgE-mediated CMA. In fact they may even be ineffective for this group. In
IgE-mediated CMA, extensively hydrolysed formula (eHF) is considered an
effective standard therapy for the majority of patients, with amino acid
formula (AAF) being reserved for associated failure to thrive or insufficient
treatment with eHF. However, in non-IgE-mediated CMA, literature and expert
opinion suggest that this formula frequently fails to resolve the symptoms. AAF
may be indicated in a large proportion of non-IgE mediated CMA. Currently, the
pathophysiology of non-Ige mediated CMA and, as a result, the most suitable
formula for these patients is not known. Preliminary data suggest that AAF has
anti-inflammatory effects on the gastrointestinal tract and therefore could do
better in comparison with eHF. The aim of this study is to compare the clinical
outcomes of early introduction of eHF versus AAF in non-IgE-mediated CMA.
Study objective
Our primary objective is to compare the clinical outcome (time to and grade of
symptom resolution) after 4-week-use of a whey based extensively hydrolysed
formula (eHF) versus an amino acid-based formula (AAF) in children with
nIgE-CMA. As secondary objectives biomarkers of (gut) inflammation, immune
status, tolerance markers, and the microbiome will be assessed and compared
between both study groups. Also, we will assess clinical characteristics of
children failing to resolve symptoms on eHF.
Study design
This study is a phase III multicentre double-blind randomized controlled trial.
Intervention
One study group will receive whey-based extensively hydrolysed formula (eHF),
the other group an amino acid-based formula (AAF). In case of insufficient
symptom resolution after 4 weeks, the study subject will be deblinded. In case
of treatment with eHF for this subject, a 4-week treatment with AAF will
follow.
Study burden and risks
Subjects participating in this study will be treated at home with the allocated
formula during four weeks. Parents will have to fill in a diary during this
treatment period. Study subjects will visit one of the study sites for the
initiation visit and after four weeks. Two weeks after the start of the study,
the coordinating investigator will make a phonecall to the parents, to evaluate
the symptoms of their child. After the treatment period, they will undergo a
double-blind placebo controlled food challenge (DBPCFC) at the hospital.
Reintroduction of the cow*s milk into the diet will be done at home according
to protocol. Follow-up visits will take place at the age of 6 and 12 months.
Blood samples will be collected at the initiation visit, after four weeks of
treatment and, dependent on the timing of the DBPCFC, at time of the food
challenge. Two samples will be collected during follow-up. The study formulas
are all approved treatments in the Netherlands and several other countries. The
total study duration will be approximately 12 weeks for each participant,
excluding the follow-up visits.
Lundlaan 6
Utrecht 3584 EA
NL
Lundlaan 6
Utrecht 3584 EA
NL
Listed location countries
Age
Inclusion criteria
- Infants *12 months of age.
- *Suspected non-IgE mediated CMA* as defined by a symptom score of at least 15
points and the pediatrician*s opinion of a possible benefit from an elimination
diet.
- Symptoms are suspected to be related to cow's milk ingestion and not
explained otherwise.
- A parental wish for formula feeding instead of a diet based on mother*s milk.
- Expected minimum *milk* intake (per day):
Birth up to 6 months: 500 ml
From 6 months to 8 months: 450 ml
From 9 months onwards: 350 ml
- Parents/Guardians are able to understand and comply with study instructions.
- Written informed consent provided by parents/ guardians, according to local
law, to participate in this study, receive allocated treatment, fill out
diaries and questionnaires and collect saliva, stool and blood samples.
Exclusion criteria
- Infants born <37 weeks gestation who require specific premature formula at
time of study entry.
- Infants less than 2500 g at birth.
- Use of any hypoallergenic formulas (partially hydrolysed formula, eHF and/or
AAF), <4 weeks prior to the first study visit, more than 1 bottle per week.
- An alternative diagnosis that is more probable than non-IgE mediated CMA (as
decided by the expert team).
- Evidence of *severe concurrent illness* (as specified in protocol).
- The use of medication (as further specified in protocol) <4 weeks prior to
the first study visit.
- Clinical history of allergy, hypersensitivity or intolerance to the
excipients of the study formulas.
Design
Recruitment
Followed up by the following (possibly more current) registration
No registrations found.
Other (possibly less up-to-date) registrations in this register
In other registers
| Register | ID |
|---|---|
| Other | Nederlands Trialregister, 7387 |
| CCMO | NL65543.041.18 |
| OMON | NL-OMON20308 |